Masayo Hasegawa

Clinical efficacy of anti-IgE therapy for eosinophilic otitis media.

Objective Eosinophilic otitis media (EOM) is an intractable otitis media characterized by a highly viscous effusion containing eosinophils, and high levels of immunoglobulin (Ig) E are detected in the middle ear effusion (MEE). We carried out a pilot study to determine whether anti-IgE therapy is efficacious in the treatment of EOM. Study Design Prospective study. Setting Tertiary referral center. Patients and Methods Eight patients with EOM received the anti-IgE agent omalizumab for at least 3 months, in addition to ordinary treatments for EOM. They were evaluated by a questionnaire for ear and respiratory symptoms, clinical scores, surrogate markers in the blood, and hearing acuity before and after the anti-IgE therapy. Nine EOM patients without anti-IgE therapy were included as controls. Results The ear symptom scores and clinical scores gradually decreased during the therapy. In particular, 5 patients who were treated for more than 1 year showed improvement of their clinical scores with resolution of the MEE. The total serum IgE level was significantly elevated after 3 months of therapy (p < 0.01). Deterioration of the bone conduction hearing levels was more frequently found in the control group than in the omalizumab group. Conclusion This pilot study provides new evidence establishing that long-term anti-IgE therapy improved the clinical ear symptoms of EOM and bone conduction hearing levels were mostly preserved. Therefore, long-term anti-IgE therapy can be effective for EOM to inhibit eosinophilic inflammation in the middle ear.

Differences in middle ear ventilation disorders between pars flaccida and pars tensa cholesteatoma in sonotubometry and patterns of tympanic and mastoid pneumatization.

Objective To investigate differences in middle ear ventilation mechanisms between pars flaccida and pars tensa cholesteatoma. Study Design Retrospective case review. Setting A referral hospital otolaryngology department. Patients Sixty-six ears with pars flaccida cholesteatoma (mean age, 45.7 yr) and 19 ears with pars tensa cholesteatoma (mean age, 58.8 yr) were included. Patients with totally adhesive tympanic membranes or mixed-type cholesteatoma were excluded. Interventions Patients underwent canal wall down tympanoplasty with canal reconstruction. The canal wall was reconstructed with tragal or conchal cartilage and cortical bone grafts. Main Outcome Measures Habitual sniffing, preoperative sonotubometry results, mastoid pneumatization (maturation), and postoperative aeration around the stapes were investigated. Preoperative mastoid pneumatization and postoperative aeration around the stapes were measured on computed tomography scans. Results Ten (15.4%) of 65 patients with pars flaccida cholesteatoma and 3 (15.7%) of 19 patients with pars tensa cholesteatoma were habitual sniffers (p = 0.5). Preoperative sonotubometry indicated that a patulous pattern was more common in ears with pars flaccida than pars tensa cholesteatoma (42.8% versus 7.1%, p < 0.05), and a stenotic pattern was more common in ears with pars tensa than pars flaccida cholesteatoma (85.8% versus 42.8%, p < 0.01). Preoperative mastoid pneumatization and postoperative aeration around the stapes were significantly better in ears with pars flaccida than pars tensa cholesteatoma (p < 0.01 and p < 0.05, respectively). Conclusion Significantly different tubal function and mastoid pneumatization patterns suggest differences in ventilation disorders and cause between ears with pars flaccida and pars tensa cholesteatoma.

Reversible cochlear function with ANCA-associated vasculitis initially diagnosed by otologic symptoms.

Objective To present 8 cases with hearing loss as an initial symptom of antineural cytoplasmic antibody (ANCA)–associated vasculitis (AAV) involving granulomatosis with polyangiitis (GPA) and to discuss the treatment and mechanisms of hearing outcomes after immunosuppressive therapy. Study Design Retrospective case review. Setting Tertiary referral center. Patients Eight patients were referred to our university hospital between 2004 and 2012 for intractable otitis media with acute progressive mixed (conductive and sensorineural) hearing loss and facial palsy. Intervention(s) Diagnostics and treatment. Main Outcome Measures Otologic symptoms as initial manifestations of otitis media with AAV and cochlear function after treatment. Results Eight cases (6 female and 2 male subjects; aged 54–73 yr; 6 MPO [myeloperoxidase]–ANCA-positive and 2 PR3 [proteinase 3]–ANCA-positive cases) were included. Progressive hearing loss was present in all patients, and facial palsy was present in 5 of 8 patients total. Patients with hearing levels better than 95 dB improved with good speech discrimination after immunosuppressive therapy, but the completely deaf could not be recovered. All patients have been successfully controlled for 1 to 8 years without any systemic disorders. Conclusion This study showed the difficulty of diagnosing localized AAV and the effectiveness of immunosuppressive therapy for hearing loss in the early stage. Based on these results, early-stage AAV would influence the stria vascularis in the cochlea. Otitis media with ANCA-associated vasculitis is a new entity among the causes of intractable otitis media and progressive hearing loss.

Relationship between postoperative aeration around the stapes and postoperative hearing outcome after canal wall down tympanoplasty with canal reconstruction for cholesteatoma.

Objectives: To evaluate the correlation between postoperative aeration around the stapes and hearing outcome after canal wall down tympanoplasty with canal reconstruction for cholesteatoma. Study Design: Retrospective case review. Setting: University hospital otolaryngology department. Patients: Seventy ears of 65 patients with middle ear cholesteatoma were included. Patients who had fixed or poorly mobile ossicular chain was excluded. Interventions: They were underwent canal wall down tympanoplasty with canal reconstruction. Canal wall was reconstructed with the tragal or conchal cartilage and the cortical bone plate. Main Outcome Measures: We measured aeration around the stapes on coronal and axial computed tomographic sections at 1 year after ossiculoplasty and investigated the correlation between postoperative aeration around the stapes and postoperative air-bone gap (using the mean of 0.5-, 1-, and 2-kHz threshold values) at 1 year after ossiculoplasty. We also investigated it for each of Wullstein type and for each of 0.25-, 0.5-, 1-, 2-, and 4-kHz thresholds. Results: Aeration around the stapes was negatively correlated with postoperative air-bone gap (correlation coefficient, -0.53; p < 0.05). Types I and IV tympanoplasty had a higher correlation with postoperative air-bone gap than type III tympanoplasty. The 0.5-KHz frequency had a higher correlation with postoperative air bone gap than other frequencies. Conclusion: Measurement of postoperative aeration around the stapes is an effective method for evaluating the importance of middle ear aeration. Aeration around the stapes contributes to better hearing outcome.

Risk factors associated with severity of eosinophilic otitis media

OBJECTIVE Eosinophilic otitis media (EOM) is an intractable otitis media associated with bronchial asthma. Clinical characteristics of EOM are apparent, but severe EOM, which is unresponsive to ongoing treatments, can occur. The present study aimed to investigate potential risk factors associated with the severity of EOM. METHODS We scored the EOM severity of 26 patients according to quantity of middle ear effusion (MEE), thickness of the middle ear mucosa, use of topical and oral corticosteroids, and use of antibiotics, all measured over a 3-month period. The scores for four 3-month periods (1 year) were averaged. We analyzed the prevalence of clinical variables by partial regression: sex, age, body mass index (BMI), duration of bronchial asthma, association of aspirin-intolerant asthma, Lund-Mackay score for sinusitis, mastoid pneumatization, width of the bony Eustachian tube at the tympanic orifice, percentage of eosinophils and immunoglobulin E in peripheral blood, and association of allergic rhinitis. Duration of bronchial asthma was defined as the period from onset of bronchial asthma to the age of first consultation at our hospital. Samples of MEE were taken for bacterial culture. RESULTS The average severity score was 6.6 (out of 16). The severity score in the pathogen-positive MEE group was significantly higher than that in the pathogen-negative MEE group (p<0.05). The score was not significantly different between the seasons. Linear multiple regression analysis showed that BMI and the duration of bronchial asthma significantly affected the EOM severity score (p<0.05). The presence of aspirin intolerant asthma tended to be correlated with the severity score. The Lund-Mackay score tended to be negatively correlated with it. CONCLUSIONS There is a significant association between the severity of EOM and obesity, as well as with the duration of bronchial asthma.

Effect of omalizumab on biomarkers in middle ear effusion in patients with eosinophilic otitis media

Abstract Conclusions: Eosinophil cationic protein (ECP) concentrations in middle ear effusion (MEE) in patients with eosinophilic otitis media (EOM) were significantly decreased at 3 months after the administration of omalizumab from the baseline level (p < 0.05). This study provides new evidence that omalizumab reduces eosinophilic inflammation in the middle ear and that the reduction of ECP may not be caused by suppression of interleukin (IL)-5 production in the middle ear mucosa. Objective: EOM is an intractable otitis media characterized by a highly viscous effusion containing eosinophils. We recently reported that anti-IgE therapy using omalizumab was efficacious in the treatment of EOM. To clarify the underlying mechanism, we determined changes in biomarkers in MEE related to eosinophilic inflammation after therapy. Methods: Nine patients with EOM received the anti-IgE agent omalizumab for 3 months. Among them, five patients continued anti-IgE therapy for longer than 1 year. Eight EOM patients without administration of omalizumab were also included in the study as controls. The concentrations of eosinophilic inflammatory markers such as ECP, IgE, IL-4, and IL-5 in MEE were measured before and after the administration of omalizumab. Results: After 3 months of omalizumab therapy, the ECP concentration in MEE was significantly reduced from the baseline level (p < 0.05), while no significant change of ECP in the serum was observed. The concentrations of IL-4 and IL-5 in MEE showed no significant change before and after the therapy in EOM patients treated with omalizumab.

A comparison of patterns of disease extension in keratosis obturans and external auditory canal cholesteatoma.

Objective To investigate the different pathways of progression to the middle ear in keratosis obturans (KO) and external auditory canal cholesteatoma (EACC). Study Design Retrospective case review. Setting Referral hospital otolaryngology department. Patients Patients with KO or EACC and middle ear disease who underwent surgical management were included. Four ears of 4 patients (mean age, 41.25 yr) were the KO group, and 5 ears of 4 patients (mean age, 49.5 yr) were the EACC group. Main Outcome Measures Intraoperative findings of the middle ear cavity were investigated in KO and EACC groups. Results In the KO group, 3 patients had a perforated tympanic membrane and cholesteatoma in the tympanic cavity. The other patient had preoperative right facial palsy. Removal of the keratin plug revealed an adherent tympanic membrane. In intraoperative findings, the tympanic segment of the fallopian canal was found to be eroded because of inflammation. No case initially progressed to the mastoid cavity. Four patients had external auditory canal cholesteatoma with middle ear disease. In EACC group, all patients had initial progression to the mastoid cavity. Conclusion KO tends to progress initially to the tympanic cavity via a diseased tympanic membrane. EACC tends to progress to the mastoid cavity via destruction of the posterior bony canal. This is the first report to investigate differences in pathway of progression to the middle ear cavity in these 2 diseases.

A comparison of preoperative characteristics of chronic otitis media in Down and non-Down syndrome.

Objective To investigate preoperative clinical findings of chronic otitis media (COM) in patients with Down and without (non-Down) syndrome. Study Design Retrospective. Setting Referral hospital, otolaryngology department. Patients Patients with COM who underwent tympanoplasty were included. There were 10 ears of 8 patients (mean age, 14.9 yr) in the Down group and 44 ears of 41 patients (mean age, 14.7 yr) in the non-Down group. Main Outcome Measures Clinical characteristics, including the frequency of preoperative persistent otorrhea, cause of COM, and mastoid pneumatization (maturation), were compared between the 2 groups using clinical records and temporal bone computed tomography (CT). Results Preoperative persistent otorrhea was more frequent in the Down group (60%) than in the non-Down group (27.2%; p < 0.05). Perforation due to tympanostomy tube insertion also occurred more frequently in the Down group (100%) than in the non-Down group (53.3%; p < 0.05). Mastoid pneumatization occurred significantly less in the Down group than in the non-Down group (p < 0.01). There was no significant difference in mastoid pneumatization regardless of the presence or absence of a past history of tympanostomy tube insertion in the Down group (p = 0.3, t test) unlike that in the non-Down group (p < 0.05, t test). All ears attained a dry condition with no perforated eardrums. Conclusion Frequent draining ear and extremely immature mastoid pneumatization, regardless of the presence or absence of a past history of tympanostomy tube insertion, were clinically important characteristics of COM in patients with Down syndrome.

Clinical characteristics and surgical benefits and problems of chronic otitis media and middle ear cholesteatoma in elderly patients older than 70 years.

Objective To investigate the benefits and problems of tympanoplasty in elderly patients older than 70 years. Study Design Retrospective case review. Setting Referral hospital otolaryngology department. Patients Among 1,014 patients who underwent tympanoplasty for chronic otitis media from 2006 to 2011, those aged over 70 years were eligible for inclusion. Main Outcome Measures Clinical characteristics including tympanosclerosis and preoperative severe complications were investigated. In chronic otitis media group, hearing outcomes (air-bone gap at 500-Hz and 1- and 2-kHz frequency) and postoperative ear condition were investigated. In chronic otitis media with cholesteatoma, clinical characteristics including postoperative bone conduction hearing threshold (at 500-Hz and 1- and 2-kHz frequency) were investigated. Results Ninety-seven ears of 83 patients were included. Eighteen ears had obvious findings of tympanosclerosis (18/97 = 18.6%). In chronic otitis media without cholesteatoma (52 ears/47 patients), no preoperative complications were noted. The mean air-bone was 30.8 and 16.1 dB before and after the operation, respectively (p < 0.001). Otorrhea disappeared in 51 ears (98.1%). In chronic otitis media with cholesteatoma (42 ears/33 patients), we noted preoperative severe complications including labyrinthine fistula (7/97 = 7.22%), widely exposed dura (1/97 = 1.03%), and facial palsy 1 (1/97 =1.03%). The mean bone conduction hearing threshold was 39.6 dB and 40.89 dB, respectively (p = 0.7). Three ears of 3 patients had operated ears with open mastoid and underwent canal wall reconstruction tympanoplasty. Conclusion Tympanoplasty in elderly patients older than 70 years seems to be as safe as when performed in younger patients.

Periostin as a novel biomarker for postoperative recurrence of chronic rhinosinitis with nasal polyps

We previously reported that chronic rhinosinusitis with nasal polyps (CRSwNP) was subdivided into four chronic rhinosinusitis (CRS) subtypes using the JESREC scoring system. We sought to identify the gene expression profile and biomarkers related with CRSwNP by RNA-sequence. RNA-sequencing was performed to identify differentially expressed genes between nasal polyps (NPs) and inferior turbinate mucosa from 6 patients with CRSwNP, and subsequently, quantitative real-time PCR was performed to verify the results. ELISA was performed to identify possible biomarkers for postoperative recurrence. In the RNA-sequencing results, periostin (POSTN) expression was the highest in NP. We focused on POSTN and investigated the protein level of POSTN by immunohistochemistry and ELISA. POSTN was diffusely expressed in moderate and severe eosinophilic CRS using immunohistochemistry, and its staining pattern was associated with the severity of the phenotype of the CRSwNP (P < 0.05). There was a significant difference between the POSTN high/low groups for postoperative recurrence when the cutoff point was set at 115.5 ng/ml (P = 0.0072). Our data suggests that the protein expression level of POSTN was associated with the severity of CRSwNP, and serum POSTN can be a novel biomarker for postoperative recurrence of CRSwNP.